For acute ischemic stroke, intravenous (IV) recombinant tissue-Plasminogen Activator (rt-PA) become the first scientifically proven and FDA-approved therapy in 1996. Despite the advance that rt-PA represents for acute stroke therapy, 50% of patients treated with rt-PA have physical disability at three months, and IV rt-PA alone opens only approximately 30-40% of arteries after one hour of treatment. In acute myocardial infarction, the addition of glycoprotein (GP) IIB/IIIa platelet receptor antagonists to fibrinolytic regimens increases the speed of arterial recanalization and the overall percentage of patients with open arteries. One small serum of patients treated with the combination of a GP IIb/IIIa antagonist and rt-PA (intra-arterial) has been reported. The Combination approach to Lysis utilizing Eptifibatide And rt-PA in acute ischemic stroke, The CLEAR Stroke channel., will be a multi-center, randomized, double-blind, sequential, dose-escalation safety study of the combination of IV eptifibatide and IV low-dose rt-PA given to acute ischemic stroke patients within 3 hours of symptom onset. The primary safety endpoint will be the incidence of symptomatic ICH within 36 hours. Patients will be randomized to a combined intravenous eptifibatide and low-dose rt-PA regimen, or a standard dose (0.9 mg/kg) rt-PA regimen in a 3 to 1 ratio. The Primary Specific Aims for this Study are: 1. To obtain reliable estimates of the safety of eptifibatide in combination with low-dose rt-PA in acute stroke patients in whom treatment is begun within three hours of symptom onset. 2. To determine if the estimated efficacy of combination therapy in acute ischemic stroke warrants proceeding to a Phase III randomized trial. 3. To obtain preliminary data regarding the potential of multi-modal MRI performed in 24 hours in providing surrogate endpoints for a phase III recanalization trial, including evaluations of vessel patency, volume of infarction, and quantitative and qualitative assessments of hemorrhagic transformation, in patients treated with combination therapy or standard dose rt-PA.